1. Field of the Invention
The present invention relates a new process for preparing of ceramide-type compounds.
2. Discussion of the Background
Ceramides, in the natural state, are the principal components of the lipid layers of the epidermis. They are used in the cosmetic field, in the natural or synthetic form, in compositions intended, inter alia, to reduce drying of the skin or to confer better elasticity on it. Alternatively, ceramides are used for the treatment of the hair.
Natural ceramides are generally obtained by extraction from pig skin, bovine brain, eggs, blood cells or plants (see, JP 86-260008 or JP 86-120308).
The disadvantages linked to this type of supply (fragility, contamination, preservation, cost and the like) meant that the chemical synthesis route was soon explored as an alternative to isolation from these natural sources.
Synthetic ceramides were thus already proposed in application EP-A-500 437. These ceramides result from the acylation of the amine functional group of a sphingosine or of a dihydrosphingosine with an activated acid, thus leading to compounds comprising an amide functional group. The acylation reactions can be carried out by numerous methods which are described by J. March in Advanced Organic Chemistry--Fourth Edition--John Wiley & Sons, Inc. p. 417-425 (1992). The activated acid used for the acylation reaction may be, for example, an acid chloride, an ester, an anhydride, an azolide and should be synthesized before carrying out the acylation reaction leading to the formation of the amide functional group of the ceramide. In addition, if the acid, in its nonactivated form, comprises one or more hydroxyl groups other than that of the carboxylic acid group, this or these hydroxyl groups should be necessarily protected so as not to react during the synthesis intended to form the amide bond. This synthesis route therefore requires a prior synthesis step of activating the acid.
It is also known from Mitchell, Reid in J. Am. Chem. Soc., Vol. 53, p. 1879 (1931) that pyrolysis of amine and acid salts can lead to amide bond formation, but this method requires several hours of heating between 160.degree. C. and 220.degree. C. The high temperature necessary for the reaction causes substantial decompositions of the starting materials or of the products formed, thus leading to low yields of synthesized products. Moreover, when amino alcohols are used as starting materials, these pyrolysis reactions predominantly lead to oxazoline-type derivatives instead of the desired ceramides.
The use of microwaves during chemical reactions of amines with acids to produce amides has been described by P. Vazquez-Tato in Synlett, 1993, p. 506. The publication by B. Oussaid, Synthetic Communications, 25(5), p. 659-665 (1995) shows that this type of reaction, carried out with 2-thienylacetic acid and ethanolamine, leads to a mixture of amide and ester, with an amide yield of 40%. A. L. Marrero-Terrero, Synlett, p. 245 (1996) shows that the reaction, carried out with .alpha.,.alpha.,.alpha.-tris(hydroxymethyl)methylamine, does not produce an amide but an oxazoline.